Symbicort in Airway Predominant Chronic Obstructive Pulmonary Disease (COPD)

Subjects from the COPDGene study who have airway-predominant COPD on chest CT scan will be enrolled; a total of 40 subjects is planned.

Subjects will all have background ipratropium-albuterol administered four times daily. Subjects will be randomized to receive budesonide (180 ug twice daily) or formoterol-budesonide (160/4.5 ug twice daily) for 12 weeks.

The main objective is to explore novel outcomes: blood biomarkers and chest CT scan. Outcomes include lung function, walk distance, respiratory disease-specific health status, and expiratory chest CT scan gas trapping as an exploratory outcome.

The primary outcome measure will be FEV1 pre-bronchodilator 12 hours after the last dose of study medication at the end of 12 weeks of treatment. FEV1 will be measured in the morning 6 hours after the last dose of ipratropium/albuterol and 12 hours after the last dose of budesonide and budesonide/formoterol

• Budesonide (Drug), also known as Pulmicort Flexhaler®: Inhaled budesonide twice daily plus inhaled ipratropium/albuterol combination four times daily and every 4 hours as needed
• budesonide/formoterol (Drug), also known as Symbicort®: Inhaled budesonide/formoterol (160/4.5 mcg Symbicort®) 2 puffs twice daily plus inhaled ipratropium/albuterol (Combivent®) 1 puff four times daily
• Ipratropium/albuterol (Drug), also known as Combivent®: Inhaled ipratropium/albuterol combination 2 puffs four times daily

Primary outcomes

• Forced expiratory volume in 1 second (FEV1) pre-bronchodilator [12 weeks]: FEV1 will be measured in the morning 6 hours after the last dose of ipratropium/albuterol and 12 hours after the last dose budesonide and budesonide/formoterol

Secondary outcomes

• Health Status [12 weeks]: Administer St. George's Respiratory Questionnaire at randomization and 12 weeks.
• Dyspnea [12 weeks]: Evaluated by the Modified Medical Research Council Dyspnea Scale at randomization and week 12.
• Six minute walk distance [12 weeks]: Evaluate six minute walk distance at randomization and 12 weeks
• Forced vital capacity (FVC) pre-bronchodilator [12 weeks]
• Post-bronchodilator FEV1 [12 weeks]
• Patient-reported exacerbations [12 weeks]
• Patient reported adverse events [12 weeks]
• Post-bronchodilator FVC [12 weeks]
• CT scan gas trapping [Before and 12 weeks after randomization]

Sex: All, ages: 45 Years to 80 Years

Inclusion Criteria:

1. COPD GOLD Stage 2 and 3 (post-bronchodilator FEV1 35-80% predicted and FEV1/FVC <0.7 at the time of enrollment in COPDGene) by spirometry.
2. Less than 15% of the lung <-950 Hounsfield Units on COPDGene high-resolution inspiratoryChest CT scan (i.e. no evidence of significant emphysema)
3. Greater than 10% gas trapping on COPDGene expiratory CT scan (i.e. evidence of small airway disease).
4. No history of recent use (within the pat 8 weeks) of an inhaled or systemic corticosteroid.
5. Body weight <100 kg (low dose CT scans in subject with increased boyd weight can not be reliably analyzed).

Exclusion Criteria:

1. Exacerbation of COPD or other respiratory illness requiring antibiotics within the past 8 weeks.
2. Previous adverse reaction to inhaled steroids, long-acting beta agonists, or long-acting anticholinergic medications.
3. Symptomatic, untreated benign prostate hypertrophy.
4. Allergy to peanuts.
5. Glaucoma

• James D Crapo, MD, Principal investigator, National Jewish Health
• Edwin K Silverman, MD, PhD, Principal investigator, Brigham and Women's Hospital
• Barry J Make, MD, Principal investigator, National Jewish Health